Profile

Research Description

The primary research purpose of this group is to understand the way in which the "professional" phagocytic cells, neutrophils, monocyte/macrophages and eosinophils, kill and digest invading microbes.
1. A central interest is the NADPH oxidase, a system responsible for the generation of superoxide and other oxygen radicals. This work involves investigation of: the flavocytochrome b electron transport chain; signal transduction mechanisms responsible for activation of superoxide production; interaction of components of the NADPH oxidase with the cytoskeleton.
2. The inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are chronic inflammatory conditions of unknown cause which primarily affect the gastrointestinal tract.
We have shown that, counter-intuitively, the acute inflammatory response and neutrophil accumulation are defective in Crohn's disease. Identification of this major phenotypic abnormality provides a significant breakthrough in understanding the pathological events that cause Crohn's disease. We are investigating how this might predispose to chronic bowel inflammation through delayed clearance of bowel bacteria penetrating the mucosa using the following approaches:
injection of 32P-labelled, heat - killed E. coli into the subcutaneous tissues of the forearm, to measure clearance as the removal of radioactivity; microarray analysis of global gene transcription profiles of monocyte/macrophages; quantitation of secretion of pro-inflammatory cytokines from monocyte/macrophages.
In line with the genetic evidence in the literature, preliminary studies in ulcerative colitis have identified a completely different abnormality in which the resolution of acute inflammation is delayed; these findings are currently under investigation.

Research Activities

Bioenergetics

Cell Biology of Phagocytes

DNA replication licensing and cell proliferation

Inflammatory Bowel Diseases

Molecular Basis of Inflammatory Bowel Diseases

Proteomics of Signal Transduction Pathways

Regulation and targeting of the hypoxia inducible factor (HIF) pathway